PROJECT SUMMARY This proposal is requesting funds to acquire a Quadrupole Orbitrap Hybrid Exploris 480 Mass Spectrometer (ThermoScientific) for the Medical University of South Carolina Mass Spectrometry Facility and Proteomics Center to support our NIH funded investigators’ efforts to discover mechanisms of protein regulation involved in cardiovascular disease, cancer, immunotherapy, digestive disease, diabetes, musculoskeletal diseases, addiction, and neurological diseases. Our users are relying on ThermoScientific Orbitrap LC-MS/MS ETD systems purchased in 2012 and 2018 (S10 OD010731 and S10 OD025126, PI: Lauren Ball) to characterize the impact of drugs/hormones, genetic alterations, and disease on changes in protein expression, protein interactions, and post-translational modifications. With the recent funding successes of new users and an increased number of NIH awards to our major user group, we are experiencing a greater demand for instrument time. To address the increased need for quantitative proteomic experiments and provide highly-sensitive, targeted-proteomic capabilities for the analysis of post-translationally modified proteins from limited amounts of sample, we are requesting the state-of-the-art Quadrupole Orbitrap Hybrid Exploris 480 MS. The requested instrumentation is to be housed in the Mass Spectrometry Facility, a University Research Resource Facility, to provide quantitative proteomic capabilities to investigators at the Medical University of South Carolina and other academic research institutions in South Carolina.